The overall aim is to examine the hypothesis that the functional behavior of sarcolemmal ionic channels underlying the electrophysiology of the heart can be altered by pathological processes such as those thought to be associated with increased arrhythmogenesis or contractile dysfunction. To assess whether channel function changes as result of cardiac pathology, enzymatically dissociated single cardiac cells derived from models of the normal and a pathologic state, that of right ventricular hypertrophy resulting from coarctation, will be employed. Cellular ionic membrane current and several of its constituent components will be characterized to assess both channel function and its response to selected interventions using the whole-cell-patch and cell-attached "loose" patch voltage-clamp techniques. We propose the following set of investigations in normal (N) and hypertrophic (H) RV myocytes. 1) A systematic characterization of both Ito and IK with emphasis on the parameters governing the currents and their frequency of appearance. 2) A search for a Ba2+-sensitive, TEA- and Ca2+ insensitive, background K current resembling "iKp", and if found, characterize it, describe the nature of the parameters governing it and determine if it is different from normal in hypertrophied myocytes. 3) Investigations of some of the characteristics of INa inactivation in both N-RV and H-RV myocytes including: (a) comparison of INa window current and its sensitivity to temperature change by newly synthesized and/or reorganized membrane of 10-15 day cultured myocytes to determine if it is the same as that elicited by freshly isolated cells using the outside-out cell- attached "loose" patch clamp technique to determine if membrane proliferation has a role in the changes in INa associated with hypertrophy membrane proliferation has a role in the changes in INa associated with hypertrophy. 4) Na-pump current and its Na+i and K+o sensitivities will be examine in hypertrophied isolated myocytes and compared to normal. This project is designed to answer some burning questions concerning the electrophysiological bases underlying the changes in the transmembrane action potential associated with ventricular hypertrophy, and could provide an electrophysiological explanation for the increased propensity for rhythm disturbances and decreased myocardial contractility associated with ventricular hypertrophy.